Functional antigen-independent synapses formed between T cells and dendritic cells

Immunological synapse formation is usually assumed to require antigen recognition by T cell receptors. However, the immunological synapse formed at the interface between naïve T cells and dendritic cells (DCs) has never been described. We show here that in the absence of antigen, and even of major histocompatibility complex molecules, T cell–DC synapses are formed and lead to several T cell responses: a local increase in tyrosine phosphorylation, small Ca2+ responses, weak proliferation and long-term survival. These responses are triggered more readily in CD4+ T cells than in CD8+ T cells, which express a specific isoform of the repulsive molecule CD43. These phenomena may play a major role in the maintenance of the naïve T cell pool in vivo.

[1]  O. Lantz,et al.  γ chain required for naïve CD4+ T cell survival but not for antigen proliferation , 2000, Nature Immunology.

[2]  D. Gray,et al.  Mice lacking MHC class II molecules , 1991, Cell.

[3]  Craig,et al.  CD 28 Ligation in T-cell Activation : Evidence for Two Signal Transduction Pathways , 2003 .

[4]  Michael L. Dustin,et al.  The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling , 2000, Nature Immunology.

[5]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[6]  A. Rudensky,et al.  Dynamic Tuning of T Cell Reactivity by Self-Peptide–Major Histocompatibility Complex Ligands , 2001, The Journal of experimental medicine.

[7]  R. Germain,et al.  CD4+ T cell survival is not directly linked to self-MHC–induced TCR signaling , 2000, Nature Immunology.

[8]  S. Tsuboi,et al.  Branched O‐linked oligosaccharides ectopically expressed in transgenic mice reduce primary T‐cell immune responses , 1997, The EMBO journal.

[9]  A. Rudensky,et al.  Survival and Homeostatic Proliferation of Naive Peripheral CD4+ T Cells in the Absence of Self Peptide:MHC Complexes1 , 2000, The Journal of Immunology.

[10]  S. Bromley,et al.  The immunological synapse: a molecular machine controlling T cell activation. , 1999, Science.

[11]  C Benoist,et al.  Tetracycline-controllable selection of CD4(+) T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. , 2000, The Journal of experimental medicine.

[12]  M. Davis,et al.  Differential clustering of CD4 and CD3zeta during T cell recognition. , 2000, Science.

[13]  A. Trautmann,et al.  Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal alterations for the triggering of an intracellular calcium response , 1998, European journal of immunology.

[14]  A. B. Lyons,et al.  Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. , 2000, Journal of immunological methods.

[15]  Philip D. Hodgkin,et al.  A cellular calculus for signal integration by T cells , 2000, Nature Immunology.

[16]  R. Vilella,et al.  CD50 (intercellular adhesion molecule 3) stimulation induces calcium mobilization and tyrosine phosphorylation through p59fyn and p56lck in Jurkat T cell line , 1994, The Journal of experimental medicine.

[17]  C. Monks,et al.  Selective modulation of protein kinase C-Θ during T-cell activation , 1997, Nature.

[18]  A. Trautmann,et al.  Imaging T‐cell antigen recognition and comparing immunological and neuronal synapses , 2001, Immunology.

[19]  T. Brocker.  Survival of Mature CD4 T Lymphocytes Is Dependent on Major Histocompatibility Complex Class II–expressing Dendritic Cells , 1997, The Journal of experimental medicine.

[20]  P. Rabinovitch,et al.  CD28 ligation in T-cell activation: evidence for two signal transduction pathways. , 1990, Blood.

[21]  C. Smith,et al.  Characterization of the activation-associated isoform of CD43 on murine T lymphocytes. , 1994, Journal of immunology.

[22]  Colin R. F. Monks,et al.  Three-dimensional segregation of supramolecular activation clusters in T cells , 1998, Nature.

[23]  L. Ellies,et al.  Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease. , 1994, Glycobiology.

[24]  P. Marrack,et al.  Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. , 1990, Science.

[25]  M. Davis,et al.  A receptor/cytoskeletal movement triggered by costimulation during T cell activation. , 1998, Science.

[26]  A. Trautmann,et al.  Antigen recognition by helper T cells elicits a sequence of distinct changes of their shape and intracellular calcium , 1994, Current Biology.

[27]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[28]  P. Rabinovitch,et al.  Role of CD2 cross‐linking in cytoplasmic calcium responses and T cell activation , 1988, European journal of immunology.

[29]  F. Lemonnier,et al.  Differential requirements for survival and proliferation of CD8 naïve or memory T cells. , 1997, Science.

[30]  H. Boehmer,et al.  Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes , 1988, Nature.

[31]  R. Flavell,et al.  CD40 and CD154 in cell-mediated immunity. , 1998, Annual review of immunology.

[32]  H. Rodewald,et al.  Class II essential for CD4 survival , 2001, Nature Immunology.

[33]  Montes,et al.  Calcium responses elicited in human T cells and dendritic cells by cell-cell interaction and soluble ligands , 1999, International immunology.

[34]  A. B. Lyons,et al.  Determination of lymphocyte division by flow cytometry. , 1994, Journal of immunological methods.

[35]  R. Germain,et al.  Response to 'Class II essential for CD4 survival' , 2001, Nature Immunology.

[36]  E. Bröcker,et al.  Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. , 2000, Immunity.

[37]  S. Kanner,et al.  Beta 2-integrin LFA-1 signaling through phospholipase C-gamma 1 activation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  A. Trautmann,et al.  Differential Roles of Lck and Itk in T Cell Response to Antigen Recognition Revealed by Calcium Imaging and Electron Microscopy1 , 2001, The Journal of Immunology.

[39]  Graça Raposo,et al.  Antigen-dependent and -independent Ca2+ Responses Triggered in T Cells by Dendritic Cells Compared with B Cells , 1998, The Journal of experimental medicine.